The aim of this proposal is to investigate and develop long-term iontophoretic procedures for delivery of narcotic agents. Iontophoresis has been known for a long time, but it application is limited to short term procedures (15-30 min.). The major impediment to long term use is the formation of electrolytic products at the electrode, lowering the efficiency of drug transport and causing complications (burns). These problems have been addressed by our group: long-term delivery has been studied both theoretically and experimentally with morphine as a model drug. As a result, treatment times have been extended up to 2 hrs with significant morphine levels in blood and no complications. The proposed study involves: 1) Laboratory in-vitro determinations of iontophoretic electrode efficiency and delivery rates over long (12-24 hrs) application times using an automated, computer controlled sampling system. 2) Animal experiments using nude rats with isolated skin flaps in order to determine long-term delivery rates with 14C morphine HCl. 3) A controlled, double blind clinical study involving patients afflicted by severe post-operative pain. In this part of the study 12 - 15 patients will be administered morphine by iontophoresis at a predetermined rate and the same number of patients will receive an iontophoretically delivered placebo. The results will be assessed statistically by comparison of frequency of IV/PCA requirements in both groups. The result of these studies will be a new iontophoretic drug delivery system for narcotic analgesics, primarily morphine. In Phase II, new electrode formulations and an iontophoretic control device will be designed, fabricated and used in large scale long-term clinical trials.